P-019: ENDOTHELIAL ACTIVATION BIOMARKERS FOR THE RISK OF CHRONIC MICROVASCULAR COMPLICATIONS IN SICKLE CELL DISEASE
Authors: AGOUTI I., MASSON E., JEAN-MIGNARD E., ARNAUD L., ABDILI E., BERENGER P., LAVOIPIERRE V., LACROIX R., BERNIT E.
Journal: HemaSphere (2022)

Purpose: Patients with sickle cell disease (SCD) are at risk for developing chronic vascular complications. The presence and the severity of these complications are not related to the severity of the vaso-occlusive disease and their pathophysiology is not completely elucidated. Circulating endothelial activation markers and their interaction may contribute to the pathophysiology of these vascular complications. In the present study, we hypothesized that plasma levels of endothelial activation markers: Circulating Endothelial Cells (CEC), E-Selectin, Progenitor’s Endothelial cells (PEC) and circulating macrovesicles (MVs), could be evaluated to characterize chronic vascular complications related to endothelial dysfunction in SCD patients. We explored the predictive value of these markers in the occurrence of disease-related microvascular injury of the eye (retinopathy), kidney (nephropathy) and skin (chronic active ulcers). Finally, we analyzed the relevance of these markers in the degree of severity of SCD and in the presence of associated thromboembolic disease (deep venous, peripheral or pulmonary thromboembolic disease). Materials and methods: Fifty patients with SCD aged 18 years or more were enrolled in this study at steady state. We investigated the relationship between plasma endothelial activation markers (CEC, E-Selectin, EPC, circulating MVs) and SCD-related microvascular complications in 3 different territories, retinopathy, nephropathy and leg ulcer. Results: Sixteen patients (32%) had SCD related retinal, renal and/or cutaneous vasculopathy. Retinopathy and nephropathy were found in 9 out of 50 and 6 out of 50 patients respectively. Three patients had leg ulcer. SCD patients with vasculopathy were older than patients without vasculopathy [37.5 (26.5-41) vs. 27.5 (21–33) years, P = 0.039]. No differences were found between patients with or without vasculopathy for sex ratio, sickle cell genotype, thromboembolic event, severe disease or hydroxyurea treatment. Among the markers of endothelial activation studied, only a significantly higher level of E-selectin was found in SCD patients with microvasculopathy (p=0.015). In subgroup analysis, patients with proliferative sickle cell retinopathy presented higher levels of E-Selectin compared to patients without retinal damage (p< 0.001). Our cohort and at steady state, whatever vasculopathy or disease severity, did not expressed high count of CEC and EPC that are markers of endothelial injury and repair. High levels of circulating Erythrocyte-MVs and Platelet-MVs were found in our SCD patients. In contrast, numbers of Leucocyte-MVs and Endothelial-MVs, respectively, were most often within the normal range. We did not shown any significant differences in MVs levels between vasculopathy and not vasculopathy SCD patients. In patients with severe vaso-occlusive disease, E-selectin level was significantly higher although other endothelial markers count were not different from SCD patients without severe disease. Patients with severe vaso-occlusive disease were significantly younger, had higher level of HbF, they more often had history of deep venous embolism and mostly treated by hydroxycarbamide. Conclusion: Our study provides evidence that circulating E-Selectin is associated with sickle cell retinopathy. Its may be considered as an accurate biological marker for endothelial involvement in SCD retinopathy. Further studies will be required to determine whether the E-Selectin could be used as an early biomarker of retinopathy sickle cell development, or even become a therapeutic target. E. BERNIT declares a conflict of interest: Consultancy, Expert: NOVARTIS PHARMA